Dental caries is initiated by the demineralization of hard tissue of the teeth usually by organic acids produced from fermentation of dietary sugar by dental plaque odontopathogenic bacteria. Dental caries is still a major public health problem. Further, restored tooth surfaces can be susceptible to further dental caries around the margins of the restoration. Even though the prevalence of dental caries has decreased through the use of fluoride in most developed countries, the disease remains a major public health problem. Dental erosion or corrosion is the loss of tooth mineral by dietary or regurgitated acids. Dental hypersensitivity is due to exposed dentinal tubules through loss of the protective mineralized layer, cementum. Dental calculus is the unwanted accretion of calcium phosphate minerals on the tooth surface. All these conditions, dental caries, dental corrosion, dental hypersensitivity and dental calculus are therefore imbalances in the level of calcium phosphates.
Fluoride-containing dentifrices and mouthrinses have been demonstrated to significantly reduce caries experience in randomized, controlled clinical trials (Biesbrock et al., 1998; Biesbrock et al., 2001; Curnow et al., 2002; Davies et al., 2002; Biesbrock et al., 2003). The efficacy of these oral care products in reducing caries activity has been attributed to their ability to incorporate fluoride ions into plaque as several investigators have suggested an inverse relationship between plaque fluoride levels and caries incidence (Duckworth et al., 1992, Duckworth and Stewart, 1994, Hartshorne et al., 1994; Skold-Larsson et al., 2000; Lynch et al., 2004).
Fluoride ions in plaque immediately promote the formation of fluorhydroxyapatite in the presence of calcium and phosphate ions produced during demineralization of tooth enamel by plaque bacterial organic acids (ten Cate, 1999). This is now believed to be the major mechanism of fluoride ion's action in preventing enamel demineralization (ten Cate, 1999; Lynch et al., 2004). However, fluoride ions can also promote the remineralization of previously demineralized enamel if enough salivary or plaque calcium and phosphate ions are available when the fluoride is applied. For every two fluoride ions, ten calcium ions and six phosphate ions are required to form one unit cell of fluorapatite. Hence on topical application of fluoride ions, the availability of calcium and phosphate ions can be rate limiting for net enamel remineralization to occur. This is highly exacerbated under xerostomic (dry mouth) conditions. Furthermore, as fluoride treatments can lead to fluorosis, particularly in children, it would be advantageous to produce dental treatment compositions having the highest efficacy for the amount of fluoride present, to reduce the overall quantity of fluoride necessary to achieve the mineralization effect.
WO 98/40406 in the name of The University of Melbourne (the contents of which are herein incorporated fully by reference) describes casein phosphopeptide-amorphous calcium phosphate complexes (CPP-ACP) and CPP-stabilised amorphous calcium fluoride phosphate complexes (CPP-ACFP) which have been produced at alkaline pH. CPP-ACP (available commercially as Recaldent™) has been shown to remineralize enamel subsurface lesions in vitro and in situ (Reynolds, 1998; Shen et al., 2001; Reynolds et al., 2003).
The CPP which are active in forming the complexes do so whether or not they are part of a full-length casein protein. Examples of active (CPP) that can be isolated after tryptic digestion of full length casein have been specified in U.S. Pat. No. 5,015,628 and include peptides Bos αs1-casein X-5P (f59-79) [1], Bos β-casein X-4P (f1-25) [2], Bos αs2-casein X-4P (f46-70) [3] and Bos αs2-casein X-4P (f1-21) [4] as follows:
[1]Gln59-Met-Glu-Ala-Glu-Ser(P)-Ile-Ser(P)-Ser(P)-Ser (P)-Glu-Glu-Ile-Val-Pro-Asn-Ser(P)-Val-Glu-Gln- Lys79 αs1(59-79) [2]Arg1-Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly-Glu-Ile- Val-Glu-Ser(P)-Leu-Ser(P)-Ser(P)-Ser(P)-Glu-Glu- Ser-Ile-Thr-Arg25 β(1-25) [3]Asn46-Ala-Asn-Glu-Glu-Glu-Tyr-Ser-Ile-Gly-Ser(P)- Ser(P)-Ser(P)-Glu-Glu-Ser(P)-Ala-Glu-Val-Ala-Thr- Glu-Glu-Val-Lys70 αs2(46-70) [4]Lys1-Asn-Thr-Met-Glu-His-Val-Ser(P)-Ser(P)-Ser(P)- Glu-Glu-Ser-Ile-Ile-Ser(P)-Gln-Glu-Thr-Tyr-Lys21 αs2(1-21)
International patent application numbers WO 03/059303 and WO 03/059304 in the name of the Procter & Gamble Company identify difficulties in maintaining measurable fluoride ions levels in oral compositions containing CPP-ACP complexes and fluoride and propose including additional components to maintain measurable fluoride levels.
It would be useful augment the remineralization activity of CPP-ACP complexes or fluoride compositions to better treat conditions such as dental caries.
It is accordingly an object of the present invention to overcome, or at least alleviate, one or more of the difficulties and/or deficiencies related to the prior art.